Abstract 3: Early, Single-Dose Post-Burn Estrogen Significantly Decreases Apoptosis at 7 Days and Pro-Inflammatory Cytokines for 45 Days in the Spleen Following Severe Burns
Introduction: In patients with severe burns, remote splenic injury is thought to be a significant contributor to immunosuppression and subsequent morbidity and mortality. We tested estrogen, a potent anti-oxidant, anti-apoptotic, and anti-inflammatory drug as a potential therapy for mitigation of splenic inflammation following severe remote burns.
Methods: 177 male rats were randomized into 3 groups: Group 1 (0.5mg/kg of 17-β estradiol (E2) SQ 15 min after injury), n=84; Group 2 (placebo), n=84; and Group 3 (sham-burn control), n=9. Groups 1 & 2 were given a 3° 40% TBSA dorsal scald burn. Eight burned/treated rats per group were sequentially sacrificed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24 hours and 7 days post-burn, with four rats/treatment sacrificed 45 days post-burn. Spleen tissue was analyzed by ELISA for proinflammatory cytokines (including IL-6, TNF-α, IL-1β). TUNEL staining was performed on the histological specimen.
Results: Administration of a single, early dose of E2 greatly decreased all measured cytokines for 45 days, as exemplified by IL-1β (see Figure), and decreased apoptosis significantly at the evaluated time point of seven days.
Conclusions: Early, single-dose estrogen administration following severe remote burns reduces the pro-inflammatory responses in the splenic tissue at all measured time points for 45 days post-burn, and significantly decreases apoptosis in the spleen at seven days. These findings help support consideration of clinical testing of estrogen as a post-burn resuscitation therapy in the future.
- © 2013 by American Heart Association, Inc.